Endocrine system hypothalamic hormones

Although it is the dominant organ of the neural system, the brain also has an endocrine function, enabling the all-important overlap between neural and endocrine control systems. The most obvious and classically recognized hormonal function of the brain arises from the peptide hormones of the hypothalamus. The hypothalamus is intimately connected with the pituitary, producing the hypothalamic-pituitary axis. The hypothalamus is part of the brain the pituitary, although located within the skull, is not part of the brain but is part of the endocrine system. Peptide hormones from the hypothalamus influence pituitary function and thus endocrine function throughout the body. 

Reports of the effects of Li+ upon the thyroid gland and its associated hormones are the most abundant of those concerned with the endocrine system. Li+ inhibits thyroid hormone release, leading to reduced levels of circulating hormone, in both psychiatric patients and healthy controls [178]. In consequence of this, a negative feedback mechanism increases the production of pituitary TSH. Li+ also causes an increase in hypothalamic thyroid-releasing hormone (TRH), probably by inhibiting its re-... 

GHRF and GHRIF are peptides secreted by hypothalamic neurons termed neuroendocrine transducers (the name is apt, as these interface between the nervous and endocrine systems). The factors that regulate their secretion are poorly understood but probably involve both nerve impulses originating from within the brain and feedback mechanisms, possibly involving pituitary hormones. 

Figure 5.2 The Hypothalamic Pituitary Axis The hypothalamus is part of the diencephalon within the brain. The pituitary, although located within the skull, is more correctly a part of the endocrine system than the nervous system. Together, the hypothalamus and pituitary form the interface between the nervous system and endocrine system and exert control over the majority of other hormone secreting organs. Releasing and inhibiting factors permit the hypothalamus to control the pituitary. Pituitary hormones are released into the general circulation, affecting metabolic function throughout the thorax and abdomen.

All the hormones produced by the anterior pituitary except prolactin (PRL) are key participants in hormonal systems in which they regulate the production by peripheral tissues of hormones that perform the ultimate regulatory functions. In these systems, the secretion of the pituitary hormone is under the control of a hypothalamic hormone. Each hypothalamic-pituitary-endocrine gland system or axis provides multiple opportunities for complex neuroendocrine regulation of growth, development, and reproductive functions. 

Thyroid hormone release is subject to the negative feedback strategy that is typical of endocrine systems controlled by the hypothalamic-pituitary axis. Increased circulating levels of the thyroid hormones (T4, T3) serve to limit their own production by inhibiting TRH release from the hypothalamus and TSH release from the anterior pituitary.30,35 This negative feedback control prevents peripheral levels of thyroid hormones from becoming excessively high. 

Hierarchical control and feedback control, both positive and negative, are a fundamental feature of endocrine systems (Figure 13.2). Each of the major hypothalamic-pituitary-hormone axes is governed by negative feedback ... 

In the brain, the hypothalamus links the nervous system to the pituitary gland (hypophysis) and this acts on the endocrine system through a number of hypothalamic hormone releasing factors neurohormones (see Chapter 10). The hypothalamus is responsible for the regulation of body temperature, hunger, and thirst and for chronobiological rhythms. 

The nervous and endocrine systems are linked by the hypothalamus which contains neurosecretory cells. These, on stimulation by electrical impulses, secrete relatively short chain highly active peptides which pass in special blood vessels directly to the pituitary gland. The hypothalamic hormones include somatostatin, which inhibits growth hormone release, and various hormones that stimulate the release of those anterior pituitary hormones that control the secretion of hormones in various other endocrine glands. For example the secretion of thyroid hormone requires... 

Figure 18.2. Endocrine-immune inter-relationship in normal subject. The hypothalamic-pituitary-adrenal (HPA) axis is a feedback loop that includes the hypothalamus, the pituitary and the adrenal glands. The main hormones that activate the HPA axis are corticotrophin releasing factor (CRF), arginine vasopressin (AVP) and adrenocorticotrophic hormone (ACTH). The loop is completed by the negative feedback of cortisol on the hypothalamus and pituitary. The simultaneous release of cortisol into the circulation has a number of effects, including elevation of blood glucose for increased metabolic demand. Cortisol also negatively affects the immune system and prevents the release of immunotransmitters. Interference from other brain regions (e.g. hippocampus and amygdala) can also modify the HPA axis, as can neuropeptides and neurotransmitters.

Figure 18.3. Endocrine-immune inter-relationship in depression. In depression, the hypothalamic-pituitary-adrenal (HPA) axis is up-regulated with a down-regulation of its negative feedback controls. Corticotrophin releasing factor (CRF) is hypersecreted from the hypothalamus and induces the release of adrenocortico-trophic hormone (ACTH) from the pituitary. ACTH interacts with receptors on adrenocortical cells and cortisol is released from the adrenal glands adrenal hypertrophy can also occur. Release of cortisol into the circulation has a number of effects, including elevation of blood glucose. The negative feedback of cortisol to the hypothalamus, pituitary and immune system is impaired. This leads to continual activation of the HPA axis and excess cortisol release. Cortisol receptors become desensitized leading to increased activity of the pro-inflammatory immune mediators and disturbances in neurotransmitter transmission.

Figure 33.2. Endocrine feedback loops of the mammalian hypothalamic-pituitary-gonadal (HPG) axis. (Adapted from La Barbera A. R. Differentiation and function of the female reproductive system. In Boekelheide, K., Chapin, R. E., Hoyer, P. B., and Harris, C. (Eds.). Comprehensive Toxicology, Vol. 10, Reproductive and Endocrine Toxicology, Elsevier, New York, 1997, pp. 255-272 and Creasy, D. M., and Foster, P. M. D. Male reproductive system. In Haschek, W. M., Rousseaux, C. G. and Wallig, M. A. (Eds.). Handbook of Toxicologic Pathology, 2nd ed., Academic Press, San Diego, 2002,pp. 785-846. E2, estradiol T, testosterone, DHT, dihydrotestosterone, FSH, follicle stimulating hormone LH, luteinizing hormone.

Examples of the use of analytical-scale column systems for the small-scale (i.e., 1 fig to 1 mg) preparative separation of peptides include the extraordinarily potent opoid peptide, dynorphin (I4S) insulin A-, B-, and C-chain peptides (24, 72) j8-chain peptides of the pituitary glycoprotein hormones (8) endorphins (28,60, 126, 137), adrenocorticotropic peptides in plasma, pituitary, and other endocrine glands or secreted from tumor cells iVt vitro (84, I2S, 127, 138, 142. I Si) hypothalamic releasing factors... 

It proved difficult to definitively demonstrate CRH synthesis from immune cells, although numerous studies provided evidence this does happen (Aird et al., 1993 Ekman et al., 1993). Eventually it became clear that regulation of CRH synthesis and release in immune cells differs from that in hypothalamic neurons. While immune cells may synthesize and release much smaller concentrations of CRH and other neuroimmune peptides, and although their release may require de novo synthesis, an inherently slow process, the fact that immune cells release these hormones locally in the target area compensates for both of these factors to some extent. These data indicating site and tissue specific effects of CRH, sometimes even contradictory effects, point to the complex interrelationship betw een the nervous, endocrine and immune systems, an interaction that has yet to be deciphered completely. 

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